Q9UBB5 (MBD2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Methyl-CpG-binding domain protein 2

Alternative name(s):
Demethylase
Short name=DMTase
Methyl-CpG-binding protein MBD2

Gene names

Name:

MBD2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	411 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Binds CpG islands in promoters where the DNA is methylated at position 5 of cytosine within CpG dinucleotides. Binds hemimethylated DNA as well. Recruits histone deacetylases and DNA methyltransferases. Acts as transcriptional repressor and plays a role in gene silencing. Functions as a scaffold protein, targeting GATAD2A and GATAD2B to chromatin to promote repression. May enhance the activation of some unmethylated cAMP-responsive promoters. Ref.1 Ref.4 Ref.5 Ref.6 Ref.7 Ref.12 Ref.14
Subunit structure	Heterodimer with MBD3. Component of the MeCP1 complex that contains HDAC1 and HDAC2. Binds DNMT1, MIZF, GPN1, SIN3A, GATAD2A/p66-alpha and GATAD2B/p66-beta. Interacts with DHX9. Ref.5 Ref.6 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.14 Ref.18
Subcellular location	Nucleus. Note: Nuclear, in discrete foci. Detected at replication foci in late S phase. Ref.1 Ref.10
Tissue specificity	Highly expressed in brain, heart, kidney, stomach, testis and placenta. Ref.4
Sequence similarities	Contains 1 MBD (methyl-CpG-binding) domain.
Caution	Functional studies (Ref.4, Ref.7 and Ref.12) have used a C-terminal fragment of isoform 1 which has been described originally as isoform MBD2b (Ref.1) but cannot however be proven by supporting cDNA sequences.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Ligand	DNA-binding
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cellular protein complex assembly Inferred from electronic annotation. Source: Compara maternal behavior Inferred from electronic annotation. Source: Compara negative regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara negative regulation of transcription, DNA-dependent Non-traceable author statement Ref.2. Source: UniProtKB positive regulation of Wnt receptor signaling pathway Inferred from electronic annotation. Source: Compara regulation of cell proliferation Inferred from electronic annotation. Source: Compara transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytoplasm Inferred from electronic annotation. Source: Compara heterochromatin Inferred from electronic annotation. Source: Compara histone deacetylase complex Inferred from electronic annotation. Source: Compara nucleus Inferred from direct assay Ref.9. Source: UniProtKB
Molecular_function	chromatin binding Inferred from electronic annotation. Source: Compara mRNA binding Inferred from electronic annotation. Source: Compara methyl-CpG binding Inferred from direct assay PubMed 21029866. Source: UniProtKB satellite DNA binding Traceable author statement Ref.1. Source: ProtInc siRNA binding Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9UBB5-1)

Also known as: MBD2a; MBD2b;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 3 (identifier: Q9UBB5-3)

The sequence of this isoform differs from the canonical sequence as follows:
     235-302: GKPDLNTTLP...SDVTEQIIKT → LRWNTHRPAP...YSRQNQSFPP
     303-411: Missing.

Note: Incomplete sequence.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 411

411

Methyl-CpG-binding domain protein 2

PRO_0000096260

Regions

Domain

145 – 213

69

MBD

Region

1 – 149

149

Necessary for interaction with DHX9

Compositional bias

6 – 140

135

Gly-rich

Compositional bias

50 – 96

47

Arg-rich

Amino acid modifications

Modified residue

181

1

Phosphoserine Ref.15 Ref.17

Modified residue

407

1

Phosphoserine Ref.13 Ref.15 Ref.16 Ref.17

Natural variations

Alternative sequence

235 – 302

68

GKPDL…QIIKT → LRWNTHRPAPWHALSRLCLL IRCLLCLECAYPLPLHLVNS YSSKTQLHCLHLWEACPAYS RQNQSFPP in isoform 3.

VSP_011077

Alternative sequence

303 – 411

109

Missing in isoform 3.

VSP_011078

Secondary structure

1

.

.

.

.

411

Helix Strand Turn

Details...

Helix

366 – 388

23

Turn

389 – 392

4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (MBD2a) (MBD2b) [UniParc]. Last modified May 1, 2000. Version 1. Checksum: FC4E5E0CF9BA0FFA	FASTA	411	43,255
	10 20 30 40 50 60 MRAHPGGGRC CPEQEEGESA AGGSGAGGDS AIEQGGQGSA LAPSPVSGVR REGARGGGRG 70 80 90 100 110 120 RGRWKQAGRG GGVCGRGRGR GRGRGRGRGR GRGRGRPPSG GSGLGGDGGG CGGGGSGGGG 130 140 150 160 170 180 APRREPVPFP SGSAGPGPRG PRATESGKRM DCPALPPGWK KEEVIRKSGL SAGKSDVYYF 190 200 210 220 230 240 SPSGKKFRSK PQLARYLGNT VDLSSFDFRT GKMMPSKLQK NKQRLRNDPL NQNKGKPDLN 250 260 270 280 290 300 TTLPIRQTAS IFKQPVTKVT NHPSNKVKSD PQRMNEQPRQ LFWEKRLQGL SASDVTEQII 310 320 330 340 350 360 KTMELPKGLQ GVGPGSNDET LLSAVASALH TSSAPITGQV SAAVEKNPAV WLNTSQPLCK 370 380 390 400 410 AFIVTDEDIR KQEERVQQVR KKLEEALMAD ILSRAADTEE MDIEMDSGDE A
	Isoform 3 [UniParc]. Checksum: CCEC65D926222717	FASTA	302	31,745
	10 20 30 40 50 60 MRAHPGGGRC CPEQEEGESA AGGSGAGGDS AIEQGGQGSA LAPSPVSGVR REGARGGGRG 70 80 90 100 110 120 RGRWKQAGRG GGVCGRGRGR GRGRGRGRGR GRGRGRPPSG GSGLGGDGGG CGGGGSGGGG 130 140 150 160 170 180 APRREPVPFP SGSAGPGPRG PRATESGKRM DCPALPPGWK KEEVIRKSGL SAGKSDVYYF 190 200 210 220 230 240 SPSGKKFRSK PQLARYLGNT VDLSSFDFRT GKMMPSKLQK NKQRLRNDPL NQNKLRWNTH 250 260 270 280 290 300 RPAPWHALSR LCLLIRCLLC LECAYPLPLH LVNSYSSKTQ LHCLHLWEAC PAYSRQNQSF PP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification and characterization of a family of mammalian methyl-CpG binding proteins." Hendrich B., Bird A. Mol. Cell. Biol. 18:6538-6547(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), NUCLEOTIDE SEQUENCE [MRNA] OF 157-411 (ISOFORM 3), FUNCTION, SUBCELLULAR LOCATION. Tissue: Testis.
[2]	"Genomic structure and chromosomal mapping of the murine and human mbd1, mbd2, mbd3, and mbd4 genes." Hendrich B., Abbott C., McQueen H., Chambers D., Cross S.H., Bird A. Mamm. Genome 10:906-912(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Lymph.
[4]	"A mammalian protein with specific demethylase activity for mCpG DNA." Bhattacharya S.K., Ramchandani S., Cervoni N., Szyf M. Nature 397:579-583(1999) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION (ISOFORM 1), TISSUE SPECIFICITY.
[5]	"MBD2 is a transcriptional repressor belonging to the MeCP1 histone deacetylase complex." Ng H.-H., Zhang Y., Hendrich B., Johnson C.A., Turner B.M., Erdjument-Bromage H., Tempst P., Reinberg D., Bird A. Nat. Genet. 23:58-61(1999) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, MASS SPECTROMETRY, INTERACTION WITH MECP1 AND HDAC1.
[6]	"MBD2-MBD3 complex binds to hemi-methylated DNA and forms a complex containing DNMT1 at the replication foci in late S phase." Tatematsu K., Yamazaki T., Ishikawa F. Genes Cells 5:677-688(2000) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, HETERODIMERIZATION WITH MBD3, INTERACTION WITH DNMT1.
[7]	"The minimal repression domain of MBD2b overlaps with the methyl-CpG-binding domain and binds directly to Sin3A." Boeke J., Ammerpohl O., Kegel S., Moehren U., Renkawitz R. J. Biol. Chem. 275:34963-34967(2000) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION (ISOFORM 1), INTERACTION WITH SIN3A.
[8]	"Stable histone deacetylase complexes distinguished by the presence of SANT domain proteins CoREST/kiaa0071 and Mta-L1." Humphrey G.W., Wang Y., Russanova V.R., Hirai T., Qin J., Nakatani Y., Howard B.H. J. Biol. Chem. 276:6817-6824(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HDAC1, MASS SPECTROMETRY.
[9]	"Involvement of a novel zinc finger protein, MIZF, in transcriptional repression by interacting with a methyl-CpG-binding protein, MBD2." Sekimata M., Takahashi A., Murakami-Sekimata A., Homma Y. J. Biol. Chem. 276:42632-42638(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH MIZF.
[10]	"Two highly related p66 proteins comprise a new family of potent transcriptional repressors interacting with MBD2 and MBD3." Brackertz M., Boeke J., Zhang R., Renkawitz R. J. Biol. Chem. 277:40958-40966(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH P66ALPHA AND P66BETA, SUBCELLULAR LOCATION.
[11]	"MBDin, a novel MBD2-interacting protein, relieves MBD2 repression potential and reactivates transcription from methylated promoters." Lembo F., Pero R., Angrisano T., Vitiello C., Iuliano R., Bruni C.B., Chiariotti L. Mol. Cell. Biol. 23:1656-1665(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH GPN1.
[12]	"Antithetic effects of MBD2a on gene regulation." Fujita H., Fujii R., Aratani S., Amano T., Fukamizu A., Nakajima T. Mol. Cell. Biol. 23:2645-2657(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH DHX9.
[13]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-407, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[14]	"p66alpha and p66beta of the Mi-2/NuRD complex mediate MBD2 and histone interaction." Brackertz M., Gong Z., Leers J., Renkawitz R. Nucleic Acids Res. 34:397-406(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH GATAD2A AND GATAD2B.
[15]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-181 AND SER-407, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[16]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-407, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[17]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-181 AND SER-407, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[18]	"p66Alpha-MBD2 coiled-coil interaction and recruitment of Mi-2 are critical for globin gene silencing by the MBD2-NuRD complex." Gnanapragasam M.N., Scarsdale J.N., Amaya M.L., Webb H.D., Desai M.A., Walavalkar N.M., Wang S.Z., Zu Zhu S., Ginder G.D., Williams D.C. Jr. Proc. Natl. Acad. Sci. U.S.A. 108:7487-7492(2011) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 360-393 IN COMPLEX WITH GATAD2A, SUBUNIT, INTERACTION WITH GATAD2A.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF072242 mRNA. Translation: AAC68871.1.
AF072246 mRNA. Translation: AAC68875.1.
AF120989, AF120988 Genomic DNA. Translation: AAD56596.1.
AF120993 , AF120988, AF120989, AF120990, AF120991, AF120992 Genomic DNA. Translation: AAD56597.1.
BC032638 mRNA. Translation: AAH32638.1.

IPI

IPI00434623.
IPI00434624.
IPI00434625.

RefSeq

NP_003918.1. NM_003927.4.
NP_056647.1. NM_015832.4.

UniGene

Hs.25674.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2L2L	NMR	-	B	360-393	[»]

ProteinModelPortal

Q9UBB5.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9UBB5. 5 interactions.

MINT

MINT-210249.

STRING

9606.ENSP00000256429.

PTM databases

PhosphoSite

Q9UBB5.

Polymorphism databases

DMDM

50401198.

Proteomic databases

PaxDb

Q9UBB5.

PRIDE

Q9UBB5.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000256429; ENSP00000256429; ENSG00000134046.
ENST00000583046; ENSP00000464554; ENSG00000134046.

GeneID

8932.

KEGG

hsa:8932.

UCSC

uc002lfg.2. human.
uc002lfh.2. human.

Organism-specific databases

CTD

8932.

GeneCards

GC18M051615.

HGNC

HGNC:6917. MBD2.

HPA

CAB037282.

MIM

603547. gene.

neXtProt

NX_Q9UBB5.

PharmGKB

PA30660.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG316386.

HOGENOM

HOG000013073.

HOVERGEN

HBG052417.

InParanoid

Q9UBB5.

KO

K11590.

OMA

DTEEVDI.

OrthoDB

EOG4GF3FS.

PhylomeDB

Q9UBB5.

Enzyme and pathway databases

Pathway_Interaction_DB

hdac_classi_pathway. Signaling events mediated by HDAC Class I.

Gene expression databases

ArrayExpress

Q9UBB5.

Bgee

Q9UBB5.

CleanEx

HS_MBD2.

Genevestigator

Q9UBB5.

GermOnline

ENSG00000134046. Homo sapiens.

Family and domain databases

Gene3D

3.30.890.10. 2 hits.

InterPro

IPR016177. DNA-bd_integrase-typ.
IPR025884. MeCpG-bd_2/3_C_dom.
IPR001739. Methyl_CpG_DNA-bd.
[Graphical view]

Pfam

PF01429. MBD. 1 hit.
PF14048. MBD_C. 1 hit.
[Graphical view]

SMART

SM00391. MBD. 1 hit.
[Graphical view]

SUPFAM

SSF54171. DNA-binding_integrase-type. 1 hit.

PROSITE

PS50982. MBD. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

MBD2. human.

DrugBank

DB01355. Hexobarbital.

GenomeRNAi

8932.

NextBio

33582.

SOURCE

Search...

Entry information

Entry name

MBD2_HUMAN

Accession

Primary (citable) accession number: Q9UBB5
Secondary accession number(s): O95242, Q9UIS8

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 19, 2004
Last sequence update:	May 1, 2000
Last modified:	May 29, 2013
This is version 113 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.